A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

Eur Heart J Cardiovasc Pharmacother. 2021 Mar 15;7(2):148-157. doi: 10.1093/ehjcvp/pvaa064.


Introduction: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies.

Methods and results: A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55).

Conclusion: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.

Keywords: Mortality; Angiotensin receptor blocker; Angiotensin-converting enzyme inhibitor; COVID-19; Clinical severity; Meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / adverse effects
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • COVID-19 / complications*
  • COVID-19 / mortality
  • Humans
  • Middle Aged
  • SARS-CoV-2*
  • Severity of Illness Index


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors